Regulation of functions of drug transporters in renal tubules by inflammatory cytokines and implication of its significance

炎症细胞因子对肾小管药物转运蛋白功能的调节及其意义

• 批准号: 23590180
• 负责人: OKUDA Masahiro
• 金额: $ 3.33万
• 依托单位: Mie University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23590180/
• 关键词: メトトレキサート; リポ多糖; ラット; 有機アニオントランスポータ; 腎クリアランス; サイトカイン; リポポリサッカライド; 腎尿細管; 尿細管分泌; 炎症; 尿細管分泌クリアランス

Plasma clearance of methotrexate (MTX) decreased about 50% in the inflammatory rat model, which is prepared by the administration of lipopolysaccharide (LPS). Involvement of glomerular filtration as well as tubular secretion were suggested in the decreased renal clearance of MTX by LPS. Renal tissue/plasma concentration ratio and efflux clearance from renal tissue to the tubular lumen also decreased in LPS rats, and were comparable to the decreased expression levels of organic anion transporters (rOAT1, rOAT3, rMRP2, rMRP4) in the kidney. In conclusion, the renal clearance of MTX markedly decreased in the LPS-treated rats and the contribution of decreased glomerular filtration as well as decreased expression levels of organic anion transporters in the renal tubules were suggested.

甲氨蝶呤（MTX）在脂多糖（LPS）诱导的炎症大鼠模型中的血浆清除率下降约50%。 LPS引起的MTX肾清除率降低与肾小球滤过和肾小管分泌有关。 在LPS大鼠中，肾组织/血浆浓度比和从肾组织到肾小管腔的外排清除率也降低，并且与肾脏中有机阴离子转运蛋白（rOAT 1、rOAT 3、rMRP 2、rMRP 4）的表达水平降低相当。 总之，MTX的肾脏清除率显着下降，在LPS处理的大鼠和肾小球滤过率下降，以及在肾小管中的有机阴离子转运蛋白的表达水平下降的贡献建议。

项目成果

miR-145による小腸上皮細胞P-糖蛋白質の転写後発現調節機構

miR-145对小肠上皮细胞P-糖蛋白转录后表达调控机制

• 发表时间: 2013
• 作者: 池村健治;山本弥里;宮崎さおり;水谷秀樹;岩本卓也;奥田真弘
• 通讯作者: 奥田真弘

Altered Pharmacokinetics of Cimetidine Caused by Down-regulation of Renal Rat Organic Cation Transporter 2 (rOCT2) after Liver Ischemia-Reperfusion Injury

• DOI: 10.2133/dmpk.dmpk-13-rg-021
• 发表时间: 2013-12-25
• 期刊: DRUG METABOLISM AND PHARMACOKINETICS
• 影响因子: 2.1
• 作者: Ikemura, Kenji;Nakagawa, Erika;Okuda, Masahiro
• 通讯作者: Okuda, Masahiro

虚血再灌流障害時における酸化ストレスを介した小腸CYP3A及びP-糖蛋白質の発現上昇によるcyclosporine Aの経口吸収低下

缺血再灌注损伤期间氧化应激导致小肠 CYP3A 和 P-糖蛋白表达增加，导致环孢素 A 口服吸收减少

• 发表时间: 2011
• 作者: 池村健治;水谷秀樹;岩本卓也;奥田真弘
• 通讯作者: 奥田真弘

Evaluation of Basophil CD203c as a Predictor of Carboplatin-Related Hypersensitivity Reaction in Patients with Gynecologic Cancer

• DOI: 10.1248/bpb.b12-00150
• 发表时间: 2012-09-01
• 期刊: BIOLOGICAL & PHARMACEUTICAL BULLETIN
• 影响因子: 2
• 作者: Iwamoto, Takuya;Yuta, Atsushi;Okuda, Masahiro
• 通讯作者: Okuda, Masahiro

miR-145 による小腸上皮細胞P-糖蛋白質の転写後発現調節機構

miR-145对小肠上皮细胞P-糖蛋白转录后表达的调控机制

• 发表时间: 2013
• 作者: 池村健治;山本弥里;宮崎さおり;水谷秀樹;岩本卓也;奥田真弘
• 通讯作者: 奥田真弘